Current position since 2007: Full Professor, Laboratory of Physical Chemistry, ETH Zurich, Switzerland and Adjunct Professor, Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA
Major Scientific Achievements:
NMR Methodology
- Nuclear Magnetic Resonance (NMR) spectroscopy is one of the major techniques for the structure and dynamics analysis of biomolecules. The Riek group has contributed in NMR method developments of studying large proteins and in the measurement of very accurate distance restraints with an accuracy of 0.1 Å, that enables the calculation of the structures of ensemble of states giving insights into protein dynamics at atomic resolution including the elucidation of concerted motion (Vögeli et al., 2012). Based on this method development insights into concerted motion of enzyme and protein allostery was elucidated (Strotz et al., 2020). In addition, the Riek group is involved in in cell NMR method development and application to elucidate the structure activity relationship in cells (Burman et al., 2020).
- Studying of Membrane Protein Structures and Dynamics
The Riek group has structurally and dynamically characterized several membrane proteins and membrane protein complexes including discoidal high density lipoprotein particles (HDL) known as the “good” cholesterol (Bibow et al.,2016). The high resolution studies allowed insight into the activity of the proteins. In addition, the interaction between the lipids and the membrane protein and the influence of the lipid composition to the dynamics of the membrane protein is studied in details (Frey et al. 2017). It has been shown that the dynamics of the lipids influences the dynamics of the protein indicating a potential source of membrane protein regulation via the membrane and its composition (such as cholesterol).
- Studying protein aggregation from a structural perspective
Protein aggregation is omnipresent in many diseases including Alzheimer’s disease and Parkinson’s disease (review by Riek and Eisenberg, 2016). The Riek group in collaboration with B. Meier (at the ETH) and H. Stahlberg (EPFL) determined several 3D structures of protein aggregates including a disease-relevant polymorph of Abeta(1-42) amyloids associated with Alzheimer’s disease (Wälti et al. 2016) using solid state NMR and alpha-synuclein fibril structures by cryo electron microscopy (Guerrero-Ferreira et al. 2018). In addition, the Riek group contributed significantly in the establishment and study of functional amyloids (review Otzen and Riek, 2019) including the elucidation of the structure-activity relationship of the prion-based immune system of HET-s being functionally and structurally conserved with mammalian necroptosis (Seuring et al. 2012), and the functional amyloid hormone storage in secretory granules establishing a structure- activity relationship for the hormone beta-endorphin, which forms reversible amyloids with pH (Seuring et al. 2020).
- On the amyloid world hypothesis
While the origin of life is unknown the RNA world hypothesis is the most prominent one while finally the peptide/protein, the membrane with its property of a compartment/container and the RNA/DNA entities must have merged. The Riek group contributed with experimental data on the hypothesis that peptide amyloids may have played a role in the origin of life by demonstrating the self replication of peptide amyloids (Rout et al. 2018), the synthesis of peptide amyloids in a prebiotic environment (Greenwald et al. 2016), and a symbiotic interplay between membranes and amyloids (Kwiatkwoski et al. 2021). Based on the proposed availability of amino acids versus nucleotides in the prebiotic soup and the simplicity of peptide amyloids composed of only several amino acid residues forming a complex 3D structure the probability of emerging life from peptide amyloids is many orders more likely than from RNA.
- On a time irreversible microscopic description of matter
The theories of physics rely usually on a time-reversible description. R. Riek elaborates on a physics theory under a discrete time and continuous space yielding amongst others an alternative description of entropy (Riek, 2012).